Postpartum depression (PPD), a common subtype of major depressive disorder, is more heritable than other psychiatric conditions, yet the genetics of PPD are understudied compared to these other psychiatric conditions, such as anxiety and bipolar disorder.
To remedy this, UNC School of Medicine researchers led an international team of researchers to conduct the largest meta-analysis of genome-wide association studies (GWAS) to date to investigate the genetic architecture of PPD.
Their research, published in the American Journal of Psychiatry, shows that about 14 per cent of the variation seen in PPD cases can be attributed to common genetic factors. A patient’s PPD is often not just the result of environmental factors, such as past trauma. Instead, PPD susceptibility has a significant genetic component.
The researchers, led by first author Jerry Guintivano, PhD, assistant professor of psychiatry at the UNC School of Medicine, also uncovered the genetic architecture of PPD, which they report correlates significantly with the genetic architecture of major depression, bipolar disorder, anxiety disorders, post-traumatic stress disorder, insomnia and polycystic ovary syndrome.
This means that PPD symptoms are likely to result from the interaction of the same genes involved in these other psychiatric and hormonal conditions.
“We looked at about 1.1 million regions of the human genome,” said Guintivano, “and we can see that PPD has a similar genetic signature to these other psychiatric conditions. The genetic risk factors for PPD appear to be shared with other disorders, such as major depression, bipolar disorder and anxiety.
The researchers also discovered that genetic regions involving GABAergic neurons are associated with PPD, particularly in the thalamus and hypothalamus. GABAergic neurons control the release of the neurotransmitter GABA.
Brexanolone, the only FDA-approved treatment for PPD, is known to circulate throughout the body and brain. UNC researchers discovered earlier this year that the drug works through GABAergic neurons to effectively treat PPD symptoms. But now this new research suggests that brexanolone likely acts on GABAergic neurons in two specific regions of the brain.
“We see our findings as a refinement of the mechanism by which brexanolone works,” said Guintivano. “We now have preliminary evidence that suggests we should target GABAergic neurons in the thalamus and hypothalamus for future research.”
Although the researchers have learned more about the genetics of PPD than ever before, they still had a limited data set. The best genome-wide association studies use data from hundreds of thousands of people with a particular condition, such as major depression or schizophrenia.
For their study, Guintivano and colleagues used 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), for a total of 18,770 PPD cases and 58,461 controls.
Although this was the largest PPD GWAS to date, Guintivano said there were still too few PPD cases to pinpoint specific locations within the genome associated with PPD risk.
